Hereditary hemochromatosis (HH) is a common disease characterized by excess iron deposition in the major organs of the body (Dadone, M. M. et al. AM. J. Clin. Pathol. 78:196–207 (1982); Edwards, C. Q. et al. N. Enql. J. Med. 18:1355–1362. (1988); McLaren, C. E., et al. Blood 86:2021–2027 (1995); Bothwell, T. H. et al., The metabolic and molecular basis of inherited disease (ed. C. R. Scriver, E. A.) 2237–2269 (McGraw-Hill, New York, 1995); Bacon, B. R. et al., Hepatoloqy. A textbook of liver disease (eds. Zakim, D. & Boyer, T. D.) 1439–1472 (W. B. Saunders, Philadelphia, 1996). A candidate gene for this disease, HFE, was identified by positional cloning (Feder, J. N., et al. Nature Genetics 13:399–408 (1996)). The gene, a novel member of the MHC class I family, was found to have a mutation, cysteine 282-->tyrosine (C282Y), in 83% of patient chromosomes (Feder, J. N., et al. Nature Genetics 13:399–408 (1996)). This mutation eliminates the ability of HFE to associate with β2-microglobulin (β2m) and prevents cell-surface expression (Feder, J. N., et al., J. Biol. Chem. 272:14025–14028 (1997)). However, the relationship of this class I-like molecule to the regulation of iron metabolism has remained obscure.
Thus, an object of the instant invention is to provide a molecular basis for the relationship of HFE to iron metabolism, and diagnostic and therapeutic agents for the treatment of iron overload diseases and iron deficiency diseases.